Murine respiratory mycoplasmosis (MRM, formerly, "chronic respiratory disease") has been and continues to be unrivaled as the major intercurrent disease problem in laboratory rodents. The net losses incurred due to MRM through wasted man hours and unusable research data are indeed staggering when one considers the continued high incidence of the disease and the fact that approximately 15,000,000 rats and 30,000,000 mice are used each year for research purposes in the United States alone. Thus, there is a critical need for practical methods to control MRM in order to reduce or eliminate the detrimental effects of this disease on the research process. Recent developments in our laboratory now permit a direct research attack on this problem. All lesions of natural MRM have been reproduced by intranasal inoculation of pure cultures of Mycoplasma pulmonis into rats and mice reared and maintained under conditions which exclude all other pathogens. Furthermore, a highly reproducible model of respiratory mycoplasmal infection has now been established both in the mouse and the rat. These models will be used in the present research program to develop a practical immunization procedure which will protect rats and mice against MRM. Several highly feasible approaches will be used in an attempt to achieve this goal, including vaccination with M. pulmonis temperature sensitive mutants, membrane components, ribosomal components, and mycoplasma L2 viruses. In parallel with these studies immune mechanisms operative in MRM will be defined so that "immunologic engineering" (cellular versus humoral immunity) can be utilized in developing an effective vaccine. Also, a reliable and rapid diagnostic procedure will be established by using new approaches to isolate mycoplasmas and by developing a rapid immunofluorescent screening technique. These studies are expected to result in control measures of immediate practical value to many investigators. In addition, knowledge gained from study of MRM in rodents is expected to contribute to the eradication and control of related diseases in various species, including man.